Genetic variations in inflammatory mediators influence lung disease progression in cystic fibrosis.

Abstract

The clinical course of cystic fibrosis (CF) varies considerably among patients carrying the same CF-causing gene mutation. Additional genetic modifiers may contribute to this variability. As airway inflammation is a key component of CF pathophysiology, we investigated whether major cytokine variants represent such modifiers in young CF patients. We tested 13 polymorphisms in 8 genes that play a key role in the inflammatory response: tumor necrosis factor, lymphotoxin alpha, interleukin (IL) 1B, IL1 receptor antagonist, IL6, IL8, IL10 and transforming growth factor beta 1 (TGFB1), for an association with lung disease progression and nutritional status in 329 CF patients. Variants in the TGFB1 gene at position +869T/C demonstrated a significant association with lung function decline. A less pronounced rate of decline in forced expiratory volume in 1 sec (FEV(1)) and forced vital capacity (FVC) were observed in patients heterozygous for TGFB1 +869 (+869CT), when compared to patients carrying either TGFB1 +869TT or +869CC genotypes. These findings support the concept that TGFB1 gene variants appear to be important genetic modifiers of lung disease progression in CF.

• Authors: Harriet Corvol, Pierre-Yves Boelle, Jacques Brouard, Nicola Knauer, Katarina Chadelat, Alexandra Henrion-Caude, Cyril Flamant, Celine Muselet-Charlier, Michele Boule, Brigitte Fauroux, Christelle Vallet, Josue Feingold, Felix Ratjen, Hartmut Grasemann, Annick Clement
• Journal: Pediatric pulmonology (Pediatr Pulmonol) Vol. 43 Issue 12 Pg. 1224-32 (Dec 2008) ISSN: 1099-0496 [Electronic] United States
• PMID: 19009622 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2008 Wiley-Liss, Inc.

Chemical References

• Inflammation Mediators
• Interleukin-1
• Interleukin-6
• Interleukin-8
• Lymphotoxin-alpha
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• Interleukin-10

Topics

• Adolescent
• Child
• Cystic Fibrosis (genetics)
• Disease Progression
• Female
• Genetic Variation
• Humans
• Inflammation Mediators (metabolism)
• Interleukin-1 (genetics)
• Interleukin-10 (genetics)
• Interleukin-6 (genetics)
• Interleukin-8 (genetics)
• Lymphotoxin-alpha (genetics)
• Male
• Transforming Growth Factor beta1 (genetics)
• Tumor Necrosis Factor-alpha (genetics)